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ATP13A2 Regulates Cellular α-Synuclein Multimerization, Membrane Association, and Externalization
Review

The Prion-Like Spreading of Alpha-Synuclein in Parkinson’s Disease: Update on Models and Hypotheses

1
Danish Research Institute of Translational Neuroscience (DANDRITE), Nordic EMBL Partnership for Molecular Medicine, Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark
2
International Diabetic Neuropathy Consortium (IDNC), Aarhus University Hospital, 8200 Aarhus, Denmark
*
Authors to whom correspondence should be addressed.
Academic Editors: Dean L. Pountney and Vladimir N. Uversky
Int. J. Mol. Sci. 2021, 22(15), 8338; https://doi.org/10.3390/ijms22158338
Received: 13 July 2021 / Revised: 29 July 2021 / Accepted: 30 July 2021 / Published: 3 August 2021
(This article belongs to the Special Issue Alpha-Synuclein in Neurodegeneration)
The pathological aggregation of the presynaptic protein α-synuclein (α-syn) and propagation through synaptically coupled neuroanatomical tracts is increasingly thought to underlie the pathophysiological progression of Parkinson’s disease (PD) and related synucleinopathies. Although the precise molecular mechanisms responsible for the spreading of pathological α-syn accumulation in the CNS are not fully understood, growing evidence suggests that de novo α-syn misfolding and/or neuronal internalization of aggregated α-syn facilitates conformational templating of endogenous α-syn monomers in a mechanism reminiscent of prions. A refined understanding of the biochemical and cellular factors mediating the pathological neuron-to-neuron propagation of misfolded α-syn will potentially elucidate the etiology of PD and unravel novel targets for therapeutic intervention. Here, we discuss recent developments on the hypothesis regarding trans-synaptic propagation of α-syn pathology in the context of neuronal vulnerability and highlight the potential utility of novel experimental models of synucleinopathies. View Full-Text
Keywords: Parkinson’s disease; alpha-synuclein; prion-like; neurodegeneration Parkinson’s disease; alpha-synuclein; prion-like; neurodegeneration
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MDPI and ACS Style

Jan, A.; Gonçalves, N.P.; Vaegter, C.B.; Jensen, P.H.; Ferreira, N. The Prion-Like Spreading of Alpha-Synuclein in Parkinson’s Disease: Update on Models and Hypotheses. Int. J. Mol. Sci. 2021, 22, 8338. https://doi.org/10.3390/ijms22158338

AMA Style

Jan A, Gonçalves NP, Vaegter CB, Jensen PH, Ferreira N. The Prion-Like Spreading of Alpha-Synuclein in Parkinson’s Disease: Update on Models and Hypotheses. International Journal of Molecular Sciences. 2021; 22(15):8338. https://doi.org/10.3390/ijms22158338

Chicago/Turabian Style

Jan, Asad, Nádia P. Gonçalves, Christian B. Vaegter, Poul H. Jensen, and Nelson Ferreira. 2021. "The Prion-Like Spreading of Alpha-Synuclein in Parkinson’s Disease: Update on Models and Hypotheses" International Journal of Molecular Sciences 22, no. 15: 8338. https://doi.org/10.3390/ijms22158338

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